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1.
Neurol Sci ; 39(5): 879-884, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29476286

RESUMO

Data regarding multiple sclerosis (MS) course in North Africans are scarce and mainly retrospective. To prospectively assess disability progression of multiple sclerosis in Tunisia. Analysis was performed in 600 patients from the MS database of the Mongi Ben Hmida National Institute of Neurology (Tunis, Tunisia), prospectively recorded over a 10-year period. Two MS phases were defined: phase 1, from MS clinical onset to Disability Status Scale (DSS) 3; and phase 2, from DSS 3 to DSS 6. Median durations of both phases and median ages at DSS 3 and DSS 6 were estimated using the Kaplan-Meier method. Median ages at DSS scores 3 and 6 were 48 years (95% confidence interval (CI), 45-50) and 53 years (95% CI, 52-55), respectively. Median time from onset to DSS 3 (phase 1 duration) was 9 years (95% CI, 7-11) and median time to DSS 6 was 12 years (95% CI, 10-15). Median phase 2 duration was 3 years (95% CI, 2.4-3.6). Males and progressive-onset patients had faster disability worsening during the first phase of the disease. Conversely, disability progression during the second phase was independent of gender and MS phenotype at onset. Our study showed that disability progression followed a two-stage process in Tunisian MS patients with however a more aggressive course compared to that in Westerners.


Assuntos
Esclerose Múltipla Crônica Progressiva/fisiopatologia , Esclerose Múltipla Recidivante-Remitente/fisiopatologia , Adulto , Idade de Início , Avaliação da Deficiência , Progressão da Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Crônica Progressiva/tratamento farmacológico , Esclerose Múltipla Crônica Progressiva/epidemiologia , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/epidemiologia , Estudos Prospectivos , Fatores Sexuais , Tunísia , Adulto Jovem
2.
Cerebellum Ataxias ; 3: 18, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27777786

RESUMO

BACKGROUND: Cerebellar ataxia represents a rare and severe complication of SjÓ§gren syndrome (SS), especially with a progressive onset and cerebellar atrophy on imaging. CASE PRESENTATION: We report the case of a 30-year-old woman, with a past history of dry eyes and mouth, who presented a severe cerebellar ataxia worsening over 4 years associated with tremor of the limbs and the head. Brain MRI showed bilateral hyperintensities on T2 and FLAIR sequences, affecting periventricular white matter, with marked cerebellar atrophy. Complementary investigations confirmed the diagnosis of primary SS (pSS). The patient was treated by methylprednisolone, Cyclophosphamid and Azathioprine. Her clinical and radiological states are stabilized after 2 years of following. Primary cerebellar degeneration is extremely rarely associated with pSS. Few cases of isolated cerebellar ataxia or belonging to a multifocal disease were reported in the literature, most of them characterized by an acute or rapidly progressive onset. Cerebellar atrophy was described in only three patients. There have been few clarifications of the pathogenesis of the neurological manifestations in pSS. Treatment is based on corticosteroids and immunosuppressive agents with no consensus of a specific therapy. CONCLUSIONS: Cerebellar ataxia due to pSS may exceptionally mimic a degenerative cerebellar ataxia, especially when the onset is progressive, which represents the particularity of our observation. The role of brain MRI and antibodies remains important for the differential diagnosis.

3.
Neurobiol Aging ; 35(5): 1125-31, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24355527

RESUMO

Parkinson disease is a progressive neurodegenerative disease for which leucine-rich repeat kinase 2 (LRRK2 carriers) p.G2019S confers substantial genotypic and population attributable risk. With informed consent, we have recruited clinical data from 778 patients from Tunisia (of which 266 have LRRK2 parkinsonism) and 580 unaffected subjects. Motor, autonomic, and cognitive assessments in idiopathic Parkinson disease and LRRK2 patients were compared with regression models. The age-associated cumulative incidence of LRRK2 parkinsonism was also estimated using case-control and family-based designs. LRRK2 parkinsonism patients had slightly less gastrointestinal dysfunction and rapid eye movement sleep disorder. Overall, disease penetrance in LRRK2 carriers was 80% by 70 years but women become affected a median 5 years younger than men. Idiopathic Parkinson disease patients with younger age at diagnosis have slower disease progression. However, age at diagnoses does not predict progression in LRRK2 parkinsonism. LRRK2 p.G2019S mutation is a useful aid to diagnosis and modifiers of disease in LRRK2 parkinsonism may aid in developing therapeutic targets.


Assuntos
Mutação , Doença de Parkinson/genética , Proteínas Serina-Treonina Quinases/genética , Fatores Etários , Idade de Início , Idoso , Estudos de Casos e Controles , Cognição , Progressão da Doença , Feminino , Humanos , Incidência , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Atividade Motora , Doença de Parkinson/diagnóstico , Doença de Parkinson/epidemiologia , Doença de Parkinson/fisiopatologia , Análise de Regressão , Risco , Fatores Sexuais
4.
Mov Disord ; 25(13): 2052-8, 2010 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-20721913

RESUMO

The LRRK2 gene is a key player in Parkinson's disease (PD), however prevalence and pathogenicity of LRRK2 variants remain to be investigated in ethnically diverse populations. Herein, we performed comprehensive sequencing of the LRRK2 gene in 92 Tunisian probands with familial PD. We then performed an association study using all identified variants in a series of 167 Lrrk2 p.G2019S-negative patients with sporadic PD and 365 Lrrk2 p.G2019S-negative healthy control subjects, all from the same Arab-Berber ethnicity. We identified one novel coding substitution (p.M2408I) and 24 known coding changes. Only the Lrrk2 p.G2019S mutation segregated with disease within families and was found in 39% of familial probands. None of the variants displayed significant association with risk for sporadic PD, however a trend was observed for Lrrk2 p.Y2189C. The present study underscores the importance of the LRRK2 gene in the Tunisian PD population.


Assuntos
Saúde da Família , Mutação de Sentido Incorreto/genética , Transtornos Parkinsonianos/genética , Proteínas Serina-Treonina Quinases/genética , Análise de Sequência de DNA , Adulto , África do Norte/etnologia , Idoso , Idoso de 80 Anos ou mais , Éxons/genética , Feminino , Genótipo , Humanos , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética
5.
J Neurol Neurosurg Psychiatry ; 81(4): 391-5, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19726410

RESUMO

Genetic classification of Parkinson's disease (PD) subtypes may become the preferred diagnostic tool for neurologists. Herein we compare clinical features from a large cohort of patients with familial PD of unknown aetiology or attributable to distinct genetic forms. Comprehensive neurological examinations were performed in 231 familial PD patients from Tunisia. Analysis was previously performed to screen for mutations in leucine rich repeat kinase 2 (LRRK2), PTEN induced kinase 1 (PINK1) and parkin (PRKN). Clinical features were compared between patients with genetically undefined PD (n=107) and those with LRRK2 (n=73) and PINK1 (n=42) mutations using regression analyses adjusted for gender, age of onset and disease duration. PRKN cases (n=9) were too few for meaningful statistical analysis. In comparison with genetically undefined patients, LRRK2 mutation carriers had more severe motor symptoms (median Unified Parkinson's Disease Rating Scale scores approximately 1.6 times higher, p<0.001), a higher rate of dyskinesia (OR 4.21, p=0.002) and use of dopamine agonists (OR 3.64, p<0.001), and less postural tremor (OR 0.21, p<0.001). PINK1 mutation carriers presented an increased rate of drug induced dyskinesia (OR 3.81, p=0.007) and a lower rate of postural tremor (OR 0.16, p<0.001) than genetically undefined patients. As expected, PINK1 patients had younger ages and ages at disease onset, and a longer disease duration compared with LRRK2 mutation carriers and genetically undefined patients. Clinical differences between LRRK2, PINK1 and genetically undefined familial PD appear more pronounced than previously appreciated, and may prove useful in clinical practice. As future therapies are targeted to specific protein abnormalities, identifying the genetic causes and associated clinical and pathological features will determine diagnosis, preventative medicine and drug intervention strategies.


Assuntos
Doença de Parkinson/genética , Proteínas Quinases/genética , Proteínas Serina-Treonina Quinases/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Programática de Saúde , Feminino , Humanos , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/complicações , Doença de Parkinson/epidemiologia , Mutação Puntual/genética , Prevalência , Tremor/diagnóstico , Tremor/etiologia , Tunísia/epidemiologia , Adulto Jovem , alfa-Sinucleína/genética
6.
Lancet Neurol ; 7(7): 591-4, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18539535

RESUMO

BACKGROUND: Several genes have been implicated in the pathogenesis of Parkinson's disease (PD). The aim of this study was to define the clinical symptoms and age-associated cumulative incidence of the most frequent mutation associated with PD, LRRK2 Gly2019Ser. METHODS: 238 patients with sporadic PD and 371 unrelated control participants from the Arab-Berber population were screened at the Institut National de Neurologie, Tunis. Symptoms of PD were assessed using the Hoehn and Yahr scale, the unified Parkinson's disease rating scale, and the Epworth scale. Genotyping for LRRK2 6055G-->A, which causes the Gly2019Ser mutation, was done in all participants, and the age-specific cumulative incidence of PD was calculated by Kaplan-Meier analysis. FINDINGS: 30% of patients with PD in this case-control sample were carriers of LRRK2 Gly2019Ser. The age of onset of symptoms and the clinical presentation of patients with LRRK2 Gly2019Ser were similar to those of patients with idiopathic PD. Carriers of LRRK2 Gly2019Ser were 22.6 times (95% CI 10.2-50.1) more likely to be affected by PD than non-carriers. Tremor was the predominant symptom in LRRK2 Gly2019Ser carriers (92% [homozygotes] vs 75% [heterozygotes] vs 69% [non-carriers]; Cochran-Armitage trend test p=0.0587). Disease severity, response to treatment, and disease duration were similar among LRRK2 Gly2019Ser homozygotes, heterozygotes, and non-carriers (p=0.85). Disease penetrance in LRRK2 Gly2019Ser carriers ranged from less than 20% in those younger than 50 years to greater than 80% at 70 years. INTERPRETATION: The LRRK2 Gly2019Ser mutation in patients with PD is a useful aid to diagnosis. LRRK2 Gly2019Ser penetrance can vary but in most carriers PD seems an inevitable consequence of ageing. LRRK2 Gly2019Ser considerably increases susceptibility to neuronal degeneration, although the process might be mediated by many triggers. By contrast, idiopathic PD is rare before 50 years and the prevalence only increases to 4% in the oldest members of the population. FUNDING: GlaxoSmithKline; National Institutes of Health; and Mayo Foundation.


Assuntos
Predisposição Genética para Doença , Glicina/genética , Doença de Parkinson/genética , Penetrância , Proteínas Serina-Treonina Quinases/genética , Serina/genética , Fatores Etários , Estudos de Casos e Controles , Frequência do Gene , Genótipo , Humanos , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina , Mutação/genética , Características de Residência , Tunísia/epidemiologia , Tunísia/etnologia
7.
J Neurogenet ; 22(2): 139-48, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18569450

RESUMO

Autosomal recessive cerebellar ataxias are a group of clinically and genetically heterogeneous neurodegenerative disorders. Growing data have shown that there is difficulty with genetic counseling in a deeply consanguineous population because of the presence of genetic heterogeneity in patients sharing similar phenotypes. The objective of this study was to report on 11 Tunisian patients belonging to the same large consanguineous family and sharing autosomal recessive ataxia phenotypes caused by three distinct gene defects. A large consanguineous Tunisian family with 11 affected patients was selected. All patients had a complete neurological examination. Blood samples were collected for molecular study. Mutation analysis revealed the presence of three distinct gene defects in the FXN (FRDA), TTPA (AVED), and SACS (ARSACS) genes within the same large family. The genetic heterogeneity observed in this family drew attention to the difficulty of genetic counseling in an inbred population and to the need for genotyping all affected members before giving genetic counseling.


Assuntos
Ataxia Cerebelar/genética , Consanguinidade , Ataxia de Friedreich/genética , Genes Recessivos/genética , Mutação/genética , Deficiência de Vitamina E/genética , Adolescente , Adulto , Idoso , Criança , Análise Mutacional de DNA , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Fenótipo
8.
Mov Disord ; 22(1): 55-61, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17115391

RESUMO

Mutations in the leucine-rich repeat kinase-2 gene (LRRK2) are responsible for some forms of familial as well as sporadic Parkinson's disease (PD). The purpose of this study was to examine the frequency of a single pathogenic mutation (6055G > A) in the kinase domain of this gene in United States and Tunisian familial PD and to compare clinical characteristics between patients with and without the mutation. Standardized case report forms were used for clinical and demographic data collection. We investigated the frequency of the most common substitution of LRRK2 (G2019S, 6055G>A) and its impact on epidemiological and phenotypic features. The frequency of mutations in Tunisian families was 42% (38/91) and in U.S. families 2.6% (1/39), with the unique opportunity to compare homozygous (n = 23) and heterozygous (n = 109) Tunisian carriers of G2019S substitutions. Individuals with G2019S substitutions had an older age at onset but few other differences compared with families negative for the substitution. Patients with LRRK2 mutations had typical clinical features of PD. Comparisons between individuals with heterozygous and homozygous LRRK2 mutations suggested that gene dosage was not correlated with phenotypic differences; however, the estimated penetrance was greater in homozygotes across all age groups.


Assuntos
Saúde da Família , Glicina/genética , Doença de Parkinson/epidemiologia , Doença de Parkinson/genética , Proteínas Serina-Treonina Quinases/genética , Serina/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Comparação Transcultural , Análise Mutacional de DNA , Feminino , Testes Genéticos/métodos , Genótipo , Humanos , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina , Masculino , Pessoa de Meia-Idade , Mutação/genética , América do Norte/epidemiologia , América do Norte/etnologia , Tunísia/epidemiologia , Tunísia/etnologia , População Branca
9.
Presse Med ; 35(11 Pt 1): 1659-1663, 2006 Nov.
Artigo em Francês | MEDLINE | ID: mdl-17086121

RESUMO

INTRODUCTION: Ureteral stenoses in Wegener's granulomatosis are rare. They usually involve the pelvic portion of the ureter and are caused by vasculitic lesions or granulomatous inflammation. CASE: A 38-year-old woman with Wegener's granulomatosis was treated with corticosteroids and monthly intravenous cyclophosphamide pulses. After 4 months, urinary retention developed, accompanied by lumbar pain, associated with protenuria and hematuria, and related to bilateral ureteral stenoses. Treatment by endoscopic dilatation and double J stents led to with clinical and radiological improvement, while the medical treatment continued. CONCLUSION: Hematuria in patients with Wegener's granulomatosis suggests renal involvement, but ureteral stenoses must also be considered when these patients present hematuria or urinary tract infections. Surgery should be reserved for those patients in whom medical treatment is not rapidly effective.


Assuntos
Granulomatose com Poliangiite/complicações , Obstrução Ureteral/complicações , Adulto , Dilatação , Feminino , Granulomatose com Poliangiite/diagnóstico por imagem , Granulomatose com Poliangiite/patologia , Humanos , Radiografia , Obstrução Ureteral/diagnóstico por imagem , Obstrução Ureteral/patologia , Obstrução Ureteral/terapia
10.
Tunis Med ; 84(12): 803-4, 2006 Dec.
Artigo em Francês | MEDLINE | ID: mdl-17288285

RESUMO

Dyslexia is a reading problem disorder. It can be a direct result of epilepsia for some kids. The researchers have done the study on 30 school kids that suffer from epilepsia. All the children had Audiometry which was normal in all cases. The orthophonic exam has done in all cases, founding a prononciation and speaker disorder also there is disorder at the psychometric test The purpose of the study research is to define the different profiles of dyslexia on the epileptics, then to check the importance of collaboration between Otorhinolaryngologists, Neurologists and Orthophonists to take care of the epileptic kids having dyslexia.


Assuntos
Dislexia/complicações , Dislexia/diagnóstico , Epilepsia/complicações , Adolescente , Criança , Feminino , Humanos , Masculino
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